DataSheet1_Complex Chromosomal Rearrangement Causes Male Azoospermia: A Case Report and Literature Review.docx

Background: Male carriers of complex chromosomal rearrangements (CCRs) may have decreased fertility and usually present with azoospermia, oligospermia or teratospermia.
Methods: High-resolution karyotype analysis using G-banding on peripheral blood lymphocytes was performed in an azoospermic male. Copy number variations (CNVs) were detected by chromosomal microarray analysis, and genetic variations were determined by long-read nanopore sequencing with Sanger sequencing for breakpoint confirmation.
Results: The karyotype of the patient was 46,XY,t(4;21)(p11;p11),t(5;6;14)(p13q22;p22q22;q22), which did not involve CNVs with clinical significance. Twelve breakpoints in chromosomes 5, 6, and 14 were found by long-read nanopore sequencing. Reports on 17 males carrying CCRs with azoospermia were also reviewed.
Conclusion: The extent of asynaptic regions in synaptonemal complexes during pachytene and the disruption of genes involved in male gametogenesis may cause azoospermia in CCR carriers.

背景：携带复杂染色体重排（complex chromosomal rearrangements, CCRs）的男性携带者可能出现生育能力下降，通常表现为无精子症、少精子症或畸精子症。
方法：对1例无精子症男性患者的外周血淋巴细胞开展G显带高分辨率核型分析。通过染色体微阵列分析检测拷贝数变异（copy number variations, CNVs），并采用长读长纳米孔测序结合Sanger测序对断裂位点进行验证以确定遗传变异。
结果：该患者的核型为46,XY,t(4;21)(p11;p11),t(5;6;14)(p13q22;p22q22;q22)，未涉及具有临床意义的拷贝数变异。长读长纳米孔测序发现5号、6号及14号染色体共存在12个断裂位点。本研究同时回顾了17例携带复杂染色体重排且表现为无精子症的男性病例报告。
结论：粗线期联会复合体中的不联会区域范围，以及参与雄性配子发生的基因发生破坏，可能是复杂染色体重排携带者出现无精子症的致病原因。